AJP - Heart and Circulatory Physiology, Vol 250, Issue 3 366-H371, Copyright © 1986 by American Physiological Society
Effects of verapamil and diltiazem on human platelet function
V. P. Addonizio Jr, C. A. Fisher, J. F. Strauss 3rd, Y. T. Wachtfogel, R. W. Colman and M. E. Josephson
In this study the antiplatelet properties of two calcium channel blockers,
verapamil and diltiazem, were evaluated. In 20 random aspirin-abstaining
donors, both diltiazem and verapamil (0.01-10 microM) reduced
epinephrine-induced aggregation [46 +/- 6% (SE) inhibition] and
demonstrated a dose-dependent inhibition of epinephrine-induced
[14C]serotonin release (43 +/- 3% reduction). However, at equimolar
concentrations, verapamil was twice as effective. Neither drug altered ADP,
collagen, thrombin, or calcium ionophore-induced platelet aggregation or
platelet granule secretion. Neither drug prevented formation of thromboxane
B2 during secondary aggregation. Verapamil, but not diltiazem, increased
the Kd of [3H]yohimbine binding from 2.03 to 46.99 nM without altering the
calculated number of binding sites per platelet (124 sites/platelet).
Supplemental calcium added to citrated platelet-rich plasma reversed both
verapamil and diltiazem-induced inhibition of platelet aggregation. We
conclude that, at the concentrations tested, both verapamil and diltiazem
are specific inhibitors of epinephrine-induced platelet activation.
Clearly, both agents may be acting by preventing epinephrine-induced
increases in plasma membrane permeability to calcium. However, the greater
potency of verapamil compared with diltiazem with only verapamil binding to
alpha2-adrenergic receptors suggests that alpha-blockade represents a
significant component of verapamil-induced platelet inhibition.
